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March 30, 2020

Evaluation of a Paradigm Shift From Intravenous Antibiotics to Oral Step-Down Therapy for the Treatment of Infective Endocarditis: A Narrative Review

Author Affiliations
  • 1Los Angeles County + University of Southern California Medical Center, Los Angeles
  • 2Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco
  • 3Infectious Disease Section, Department of Medicine, Baylor College of Medicine, Houston, Texas
  • 4Division of Infectious Diseases, Allegheny General Hospital, Pittsburgh, Pennsylvania
  • 5Division of Infectious Diseases, The Lundquist Institute for Biomedical Innovation, Torrance, California
  • 6The Geffen School of Medicine, University of California, Los Angeles
JAMA Intern Med. 2020;180(5):769-777. doi:10.1001/jamainternmed.2020.0555

Importance  The requirement of prolonged intravenous antibiotic courses to treat infective endocarditis (IE) is a time-honored dogma of medicine. However, numerous antibiotics are now available that achieve adequate levels in the blood after oral administration to kill bacteria. Moreover, prolonged intravenous antibiotic regimens are associated with high rates of adverse events. Accordingly, recent studies of oral step-down antibiotic treatment have stimulated a reevaluation of the need for intravenous-only therapy for IE.

Observations  PubMed was reviewed in October 2019, with an update in February 2020, to determine whether evidence supports the notion that oral step-down antibiotic therapy for IE is associated with inferior outcomes compared with intravenous-only therapy. The search identified 21 observational studies evaluating the effectiveness of oral antibiotics for treating IE, typically after an initial course of intravenous therapy; none found such oral step-down therapy to be inferior to intravenous-only therapy. Multiple studies described an improved clinical cure rate and an improved mortality rate among patients treated with oral step-down vs intravenous-only antibiotic therapy. Three randomized clinical trials also demonstrated that oral step-down antibiotic therapy is at least as effective as intravenous-only therapy in right-sided, left-sided, or prosthetic valve IE. In the largest trial, at 3.5 years of follow-up, patients randomized to receive oral step-down antibiotic therapy had a significantly improved cure rate and mortality rate compared with those who received intravenous-only therapy.

Conclusions and Relevance  This review found ample data demonstrating the therapeutic effectiveness of oral step-down vs intravenous-only antibiotic therapy for IE, and no contrary data were identified. The use of highly orally bioavailable antibiotics as step-down therapy for IE, after clearing bacteremia and achieving clinical stability with intravenous regimens, should be incorporated into clinical practice.

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